Analytical operations, particularly bioanalytical operations, have been subject to major advancements over the past thirty years, e.g., the advent of powerful analytical and manipulation techniques such as the polymerase chain reaction, recombinant DNA technology, rapid sequencing methods, and microfluidic analysis systems. However, a need still exists for greater sensitivity and specificity, higher accuracy, e.g., for kinetic analysis, greater reproducibility, and more rapid and cost-effective analytical systems.
For example, in drug discovery, large panels of molecules are often tested for their ability to modulate (e.g., inhibit or potentiate) an enzyme that is implicated in a pathological process. In addition, the ability to monitor cellular responses is important in a number of areas, such as biological research and drug discovery. For example, monitoring activity of potential anti-cancer agents and their effect on a specific cell type is critical in determining its efficacy and/or potential toxicity. Typical assays can involve incorporation and/or removal of radioactive or fluorescent labels and are time consuming, in addition to lacking sensitivity. In addition, various technologies, e.g., patch clamp, voltammetry, amperometry, fluorescence microscopy, capillary electrophoresis, e.g., with fluorescence and/or electrochemical labels, and the like, have been developed to address monitoring and detection of cellular responses and transport. However, none of the techniques is capable of real time monitoring or detection of a change in a single cell at a single molecular level. In addition, the techniques presently available do not offer a microarray format that is suitable to high throughput screening.
Furthermore, chemical sensing technologies have been developed using chemically sensitive field effect transistors, or chem-FETs, to detect the presence and/or concentration of a variety of chemical and biochemical species. These sensors employ electrical signals, as opposed to optical signals, which provide a sensitive means for detection of many analytes without the use of labels, e.g., expensive and/or potentially interfering labels. However, chem-FETs still suffer from low sensitivity.
Therefore, a need exists for a simple method that allows the detection of an analyte of interest and/or analysis of cellular behavior using a sensitive, non-invasive, label-free system that could be carried out on multiple samples in a rapid and cost-effective manner. The present invention fulfills these and other needs related to chemical, biochemical, and cellular detection.